The genomes of human tumors contain many sequence alterations, a subset of which help drive tumor growth. Wood et al. (see Perspective by Trent and Touchman) have now undertaken a systematic sequence analysis of >18,000 genes in human breast and colorectal tumors. Depiction of the mutational data on a topographic map indicates that each of these tumor types contains only a few gene "mountains" mutated at high frequency and a much larger number of gene "hills" mutated at low frequency. Importantly, while a large fraction of the mutations driving tumor growth reside in the gene hills rather than the mountains--a finding that underscores the heterogeneity of human cancer--it appears that many of the mutated genes function through cellular signaling pathways that are already well known.